The invention relates to the determination of the partial pressure of at least one gas in extracorporeally flowing blood in which the gas or gases are separated from the blood in a membrane filter and then brought into contact with at least one sensor responsive to such gas partial pressure.
The invention also relates to an apparatus for determining the partial pressures of gases in the blood comprising a filter, which is divided by a semipermeable membrane into two chambers, an extracorporeal blood conducting system conducted with one of the chambers and at least one sensor for measuring the partial pressure of the gas and which is connected by a duct with the other of the chambers of the filter.
Continuous monitoring of the acid-base parameters in the blood is particularly important during operations in which the patient is connected with a heart-lung machine and also during extracorporeal membrane oxygenation (ECMO). During such a procedure the partial pressures of oxygen and carbon dioxide are measured together with the pH value.
Furthermore, determination of these parameters upstream and downstream of the oxygenator is important for assessing the efficacy, or any drop in efficiency, of the oxygenator. Thus it is possible to distinguish between a change in the partial pressure of the blood due to a decrease in efficiency of the oxygenator and a change which is caused metabolically.
In order to obtain such data the normal course is to take occasional samples from the extracorporeal blood flow and then to analyze them in a blood gas analyzer. Such a procedure does however involve a substantial expense as regards staffing and equipment. For this reason sensors have been developed which are directly incorporated in the extracorporeal blood flow system and thus come into direct contact with the blood so that the blood gases may be continuously recorded in the extracorporeal blood flow system.
In connection with the use of such continuously operating sensors coming into direct contact with the blood, there is a calibration problem insofar as both the null point and also the slope of the response characteristic of such sensors may drift comparatively rapidly. It is more especially the case of cardiac operations lasting a matter of hours, or of ECMO lasting several days, that there is a serious problem here, since it is then not possible to obtain any reliable data.
Furthermore the direct connection of such sensors with an extracorporeal blood circuit tends to be problematical because there may be an interaction of the blood with the surface of the sensor and there is a risk of the sensitive surface of the sensor becoming clogged with a layer of blood components, that is to say the surface will be obscured by deposits and the data will be false.
In order to deal with this possibility procedures have been evolved in which the sensors were calibrated by the normal method prior to the treatment of the patient and samples were then taken at intervals during the treatment so that they might then be checked in a conventional blood gas analyzer. Apart from certain method errors and its complexity, this procedure did not make it possible to check or correct the slope of the response function of the sensor, because, for this to be done, two measurements at different partial pressure would be needed.
Moreover, in the case of such treatment making use of an extracorporeal circuit there is the necessity of measuring the concentrations of the blood electrolytes, something involving the taking of further samples.
An example in this respect is to be seen in an article in Biomedical Business International, Dec-12, 1985, Vol. VIII, No. 23/24, page 232 describing a device able to continuously measure not only blood gases but also electrolytes. For this purpose a continuously operating sampling device takes a small amount of the blood from the extracorporeal circuit or from the patient directly so that it may be continuously analyzed in the analyzer. This operation may be automatically interrupted at certain intervals, whereupon calibration solution is supplied to the device via valve means for renewed adjustment.
However it is a disadvantage in this respect that sampling is directly from the extracorporeal circuit or from the body of the patient since this will involve sterility problems. A further point is that entire blood is taken from the circuit which has to be conditioned with a sufficient amount of a clotting inhibitor so that the very act of adding such substance to the entire blood means that the gas equilibrium in the sample will be interfered with and the results of measurement falsified.
All in all, this previously proposed device involves an increased risk of contamination by the direct connection of the sampling device with the extracorporeal circuit.
It is furthermore stated in standard literature on the subject (see Oswald Mueller-Plathe: Saeure-Basen-Haushalt und Blutgase, second edition, Klinische Chemie by Einzeldarstellungen, Vol. 1, H. Breuer, H. Buettner, D. Stamm, published by Georg Thieme-Verlag, Stuttgart, 1982, page 148 et seq.) that the generally held opinion is that the determination of blood gases in plasma or serum leads to serious errors of measurement. In fact even a short time after the taking of a sample and separation of the red blood corpuscles, the oxygen partial pressure determined will be equal to the oxygen partial pressure in the atmosphere, because for separation of the erythrocytes and obtaining the plasma the entire blood is treated for some minutes in a centrifuge, the supernatant plasma then being drawn off with a syringe and being analyzed at once in a blood gas analyzer. However it has been found that even after a short centrifuging period the oxygen level will have risen by a factor of 2 to 3. Furthermore the carbon dioxide partial pressure will fall by approximately 20%, this corresponding to an increase in the pH value.
Accordingly the view has been taken so far that the determination of blood gases in plasma would not serve any useful purpose.
The German unexamined specification No. 2,725,757 describes a device of the initially mentioned type in which the blood is caused to pass through a dialysis filter, whose other side has a dialyzing liquid flowing through it. The substances to be determined diffuse through the pores of the membrane of the dialysis filter from the blood side to the dialyzing liquid side where they are conveyed with the dialyzing liquid to the analyzer. In order to make possible any form of quantitative determination it would be necessary for all method parameters to be kept constant, but this is not possible; for example the membrane becomes clogged with a secondary layer of proteins on the blood side and this increases the diffusion resistance by a factor of up to 5. A further varying parameter is the change in the electrolyte content of the blood from sample to sample even during the measuring period so that there are concentration gradients between the blood and dialysis liquid sides of the device. This also has a considerable interfering effect on the measuring operation.
A further point to be considered is that the blood and also the dialysis liquid have to be caused to pass through the dialysis filter at maximum velocity in order to avoid falsification in the concentration of the subtances to be determined. If, as is normally the case, peristaltic pumps are used, this will not be possible owing to pulsations which occur.
Since the diffusion of the substances to be determined is of paramount importance in the measuring operation, during calibration as well suitable calibrating solutions have to be supplied to the extracorporeal circuit, something which meets with intractable problems as regards cleaning and safefy. Furthermore the supply of such calibration solutions means that the protein layers deposited on the membrane surfaces will be removed again and this necessarily leads to a falsification of the measured data.